The overall aims of this proposal are to produce and characterise new mutant mouse strains that will be applicable to the study of diseases and biology of the gut and allow the identification of genes involved in regulating these processes. Inflammatory diseases of the gut including ulcerative colitis, Crohn's disease and gastritis are the result of a destructive inflammatory response. Despite recent advances, the basis for these diseases remains unclear and we know little about the normal molecular mechanisms that control inflammation in the gut. The events that underlie the cell development in gut epithelia are poorly understood, as are the pathological outcomes of aberrant development that frequently develop into cancer. To identify new animal models that address these issues a screen of mice that have been mutated with a chemical has been initiated. This approach has been used very successfully to discover genes that control disease and development in other organ systems. The entire gut will be examined in these mutant mice to detect abnormalities that mimic human disease. Once located the positions and identities of the mutated genes will be determined. To our knowledge, no other laboratories in the world are screening for gut disease mutants in the manner described here, and therefore we have a strong competitive advantage in detecting and developing new mouse models of gut disease.Project Narrative Diseases of the gut including inflammatory bowel disease, bowel cancer and stomach cancer are major health problems affecting many millions of people world-wide. This project seeks to discover new models for these diseases and the pathological conditions that predispose to them, and which will facilitate a greater understanding of these conditions and the development of new treatments.